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Reduced LRRK2-positive neurons in the striatum of Parkinson’s disease patients hypothesize a retrograde disease mechanism?

Basal Ganglia, ISSN: 2210-5336, Vol: 2, Issue: 2, Page: 67-72
2012
  • 2
    Citations
  • 0
    Usage
  • 10
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    2
    • Citation Indexes
      2
  • Captures
    10

Article Description

One major unsolved question in leucine-rich repeat kinase 2 (LRRK2)-mediated dopaminergic degeneration in Parkinson disease (PD) is the discrepancy between the preferentially diseased neuron type (dopamine neurons within substantia nigra ) and the expression pattern of LRRK2 (highest expression within dopamine neuron target areas, striatum). We investigated LRRK2 mRNA and protein expression pattern in the Substantia nigra pars compacta as well as the striatum ( caudate nucleus ) in human brain specimens of sporadic PD patients ( n = 10) and age-matched controls ( n = 14). We did not find any differences in healthy and diseased Substantia nigra pars compacta with no detectable LRRK2 protein expression in dopamine neurons in both conditions. Contrary, we observed a significant reduction of LRRK2-immunoreactive neurons in the striatum in PD compared to controls. Our data question a cell-intrinsic pathophysiological role of LRRK2 in Substantia nigra pars compacta dopamine neurons, but might indicate a role of LRRK2 in retrograde deterioration of dopamine neurons coming out of their projection area.

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